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Home › Research › Genetics

A human brain vascular atlas reveals diverse mediators of Alzheimer's risk

Yang AC, Vest RT, Kern F, Lee DP, Agam M, Maat CA, Losada PM, Chen MB et al.. Nature, 2022-02-14

This page is alzhub.org's plain-English summary of a published study, not the paper itself. It is generated from the record we hold for this study, sourced and linked below — check the original for the full text and methods.

✓ Peer-reviewed alzhub usefulness score 45 out of 100. Genetics

Topic: Genetics and APOE

The human brain vasculature is of great medical importance: its dysfunction causes disability and death 1 , and the specialized structure it forms-the blood-brain barrier-impedes the treatment of nearly all brain disorders 2,3 . Yet so far, we have no molecular map of the human brain vasculature. Here we develop vessel isolation and nuclei extraction for sequencing (VINE-seq) to profile the major vascular and perivascular cell types of the human brain through 143,793 single-nucleus transcriptomes from 25 hippocampus and cortex samples of 9 individuals with Alzheimer's disease and 8 individuals with no cognitive impairment. We identify brain-region- and species-enriched genes and pathways. We reveal molecular principles of human arteriovenous organization, recapitulating a gradual endothelial and punctuated mural cell continuum. We discover two subtypes of human pericytes, marked by solute transport and extracellular matrix (ECM) organization; and define perivascular versus meningeal fibroblast specialization. In Alzheimer's disease, we observe selective vulnerability of ECM-maintaining pericytes and gene expression patterns that implicate dysregulated blood flow. With an expanded survey of brain cell types, we find that 30 of the top 45 genes that have been linked to Alzheimer's disease risk by genome-wide association studies (GWASs) are expressed in the human brain vasculature, and we confirm this by immunostaining. Vascular GWAS genes map to endothelial protein transport, adaptive immune and ECM pathways. Many are microglia-specific in mice, suggesting a partial evolutionary transfer of Alzheimer's disease risk. Our work uncovers the molecular basis of the human brain vasculature, which will inform our understanding of overall brain health, disease and therapy.

Key findings

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Study details

How this study scored 45/100
How this study's score is builtJournal tier 10 of 10; Journal's citation record left out, no data; Study design 0 of 12; Strength of evidence 1 of 5; Peer-review validation 10 of 10; How recent 3 of 5; Sample size 0 of 4; Effect reported 0 of 3; Studied in people 0 of 3; Randomised / blinded 0 of 2; Times cited left out, no data; Citations per year left out, no data; Impact for its field and year left out, no data; Cited by studies here left out, no data; Still being cited left out, no data; Senior author's track record left out, no data; Institution's track record left out, no data; Multi-centre collaboration left out, no data; Indexed in PubMed 2 of 2; Free to read 0 of 2. 26 of the 58 points it could be judged on, which is 45 of 100. Total 45 of 100.26 of the 58 points we could judge = 45 of 100

Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 26 of the 58 points we could judge it on, which is 45 out of 100.

ComponentPointsWhy
Journal tier 10 / 10 Tier 1 — top-tier general journal (Nature)
Journal's citation record — / 4 No journal record from OpenAlex — left out of this score
Study design 0 / 12 No study design recorded — scores zero, not guessed (not stated in the record — scored 0)
Strength of evidence 1 / 5 Rated “low” in our summary
Peer-review validation 10 / 10 Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent 3 / 5 2022 — within 6 year(s) of the newest study here
Sample size 0 / 4 Participant count not stated — scores zero (not stated in the record — scored 0)
Effect reported 0 / 3 No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people 0 / 3 Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomised / blinded 0 / 2 No randomisation or blinding stated — scores zero (not stated in the record — scored 0)
Times cited — / 7 No citation count (not found in OpenAlex) — left out of this score
Citations per year — / 5 No citation count or no year — left out of this score
Impact for its field and year — / 6 No field-weighted citation impact (OpenAlex has none yet) — left out of this score
Cited by studies here — / 6 Not yet checked against this library's citation graph — left out of this score
Still being cited — / 4 No yearly citation counts — left out of this score
Senior author's track record — / 4 Senior author's record not available — left out of this score
Institution's track record — / 3 No institution listed in OpenAlex — left out of this score
Multi-centre collaboration — / 3 Institutions not listed — left out of this score
Indexed in PubMed 2 / 2 Indexed in PubMed (PMID 35165441)
Free to read 0 / 2 Behind a paywall — scores zero
Points 26 / 58 Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100.
Total 45 / 100 —

What each of these 20 components measures, and what this score is not →

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Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.

APA 7th

Yang, A. C., Vest, R. T., Kern, F., Lee, D. P., Agam, M., Maat, C. A., et al. (2022). A human brain vascular atlas reveals diverse mediators of Alzheimer's risk. Nature. https://doi.org/10.1038/s41586-021-04369-3

Vancouver

Yang AC, Vest RT, Kern F, Lee DP, Agam M, Maat CA, et al. A human brain vascular atlas reveals diverse mediators of Alzheimer's risk. Nature. 2022. doi:10.1038/s41586-021-04369-3. PMID: 35165441.

BibTeX

@article{yang2022-35165441,
  author  = {Yang, A. C. and Vest, R. T. and Kern, F. and Lee, D. P. and Agam, M. and Maat, C. A. and Losada, P. M. and Chen, M. B. and others},
  title   = {{A human brain vascular atlas reveals diverse mediators of Alzheimer's risk}},
  journal = {Nature},
  year    = {2022},
  doi     = {10.1038/s41586-021-04369-3},
  pmid    = {35165441},
  url     = {https://doi.org/10.1038/s41586-021-04369-3}
}

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